Immunomodulatory Effect of Phytoactive Compounds on Human Health: A Narrative Review Integrated with Bioinformatics Approach.

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: To understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259 indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Nutrient Homeostasis of Aegilops Accessions Differing in B Tolerance Level under Boron Toxic Growth Conditions.

Boron (B) is a crucial microelement for several biological processes in plants; however, it becomes hazardous when present in excess in the soil. B toxicity adversely affects the wheat yield all around the world, particularly in the arid and semiarid regions. Aegilops, the nearest wild wheat relatives, could be an efficient source to develop B toxicity tolerance in modern cultivars. However, to potentially utilize these species, it is necessary to understand the underlying mechanisms that are involved in providing them tolerance. Other than hampering cellular and physiological activities, high B inhibits the uptake of nutrients in wheat plants that lead to nutrients deficiency causing a hindered growth. Thus, it is crucial to determine the effect of B toxicity on nutrient uptake and finally, to understand the role of nutrient homeostasis in developing the adaptive mechanism in tolerant species. Unfortunately, none of the studies to date has explored the effect of high B supply on the nutrient uptake in B toxicity tolerant wild wheat species. In this study, we explored the effect of 1 mM B (toxic B), and 10 mM B (very toxic B) B on the nutrient uptake in 19 Aegilops genotypes differing in B tolerance in contrast to Bolal 2973, the familiar B tolerant genotype. The obtained outcomes suggested a significant association between the B toxicity tolerance and the level of nutrient uptake in different genotypes. The B toxicity tolerant genotypes, Ab2 (TGB 026219, A. biuncialis genotype) and Ac4 (TGB 000107, A. columnaris genotype) were clustered together in the nutrient homeostasis-based heat map. Though B toxicity mostly had an inhibitory effect on the uptake of nutrients in root-shoot tissues, the tolerant genotypes revealed an increase in nutrient uptake under B toxicity in contrast with Control. The study directs towards future research where the role of external supply of few nutrients in enhancing the B toxicity tolerance of susceptible genotypes can be studied. Moreover, the genotype-dependent variation in the nutrient profile of the studied Aegilops genotypes under high B suggested that increasing number of Aegilops germplasm should be screened for B toxicity tolerance for their successful inclusion in the pre-breeding programs focusing on this issue.

Insight into the Prospects for Nanotechnology in Wheat Biofortification.

The deficiency of nutrients in food crops is a major issue affecting the health of human beings, mainly in underdeveloped areas. Despite the development in the methods of food fortification, several barriers such as lack of proper regulations and smaller public-private partnerships hinder its successful implementation in society. Consequently, genetic and agronomic biofortification has been suggested as the potential techniques for fortifying the nutrients in diets. However, the time-consuming nature and restricted available diversity in the targeted crop gene pool limit the benefits of genetic biofortification. In agronomic biofortification, organic fertilizers face the problem of prolonged duration of nutrients release and lesser content of minerals; while in inorganic fertilizers, the large-sized fertilizers (greater than 100 nm) suffer from volatilization and leaching losses. The application of nanotechnology in agriculture holds enormous potential to cope with these challenges. The utility of nanomaterials for wheat biofortification gains its importance by supplying the appropriate dose of fertilizer at the appropriate time diminishing the environmental concerns and smoothening the process of nutrient uptake and absorption. Wheat is a major crop whose nano-biofortification can largely handle the issue of malnutrition and nutrients deficiency in human beings. Though several research experiments have been conducted at small levels to see the effects of nano-biofortification on wheat plants, a review article providing an overview of such studies and summarizing the benefits and outcomes of wheat nano-biofortification is still lacking. Although a number of review articles are available on the role of nanotechnology in wheat crop, these are mostly focused on the role of nanoparticles in alleviating biotic and abiotic stress conditions in wheat. None of them focused on the prospects of nanotechnology for wheat biofortification. Hence, in this review for the first time, the current advancement in the employment of different nanotechnology-based approaches for wheat biofortification has been outlined. Different strategies including the supply of nano-based macro- and micronutrients that have shown promising results for wheat improvement have been discussed in detail. Understanding several aspects related to the safe usage of nanomaterials and their future perspectives may enhance their successful utilization in terms of economy and fulfillment of nutritional requirements following wheat nano-biofortification.

Variability in Physiological Traits Reveals Boron Toxicity Tolerance in Aegilops Species.

Boron (B) is an important micronutrient required for the normal growth and development of plants. However, its excess in the soil causes severe damage to plant tissues, which affects the final yield. Wheat, one of the main staple crops, has been reported to be largely affected by B toxicity stress in arid and semi-arid regions of the world. The prevalence of B toxicity stress can be addressed by utilizing wild wheat genotypes with a variant level of stress tolerance. Wild wheat relatives have been identified as a prominent source of several abiotic stress-tolerant genes. However, Aegilops species in the tertiary gene pool of wheat have not been well exploited as a source of B toxicity tolerance. This study explores the root and shoot growth, proline induction, and extent of lipid peroxidation in 19 Aegilops accessions comprising 6 different species and the B-tolerant check wheat cultivar Bolal 2973 grown under Control (3.1 µM B), toxic (1 mM B), and highly toxic (10 mM B) B stress treatment. B toxicity stress had a more decisive impact on growth parameters as compared to the malondialdehyde (MDA) and proline content. The obtained results suggested that even the genotypes with high shoot B (SB) accumulation can be tolerant to B toxicity stress, and the mechanism of B redistribution in leaves should be studied in detail. It has been proposed that the studied Aegilops accessions can be potentially used for genetically improving the B toxicity-tolerance trait due to a high level of variation in the response toward high B toxicity. Though a number of accessions showed suppression in the root and shoot growth, very few accessions with stress adaptive plasticity to B toxicity stress leading to an improvement of shoot growth parameters could be determined. The two accessions, Aegilops biuncialis accession TGB 026219 and Aegilops columnaris accession TGB 000107, were identified as the potential genotypes with B toxicity stress tolerance and can be utilized for developing a pre-breeding material in B tolerance-based breeding programs.

Natural Plant Products: A Less Focused Aspect for the COVID-19 Viral Outbreak.

The sudden emergence of COVID-19 caused by a novel coronavirus (nCoV) led the entire world to search for relevant solutions to fight the pandemic. Although continuous trials are being conducted to develop precise vaccines and therapeutic antibodies, a potential remedy is yet to be developed. Plants have largely contributed to the treatment of several human diseases and different phytoconstituents have been previously described to impede the replication of numerous viruses. Despite the previous positive reports of plant-based medications, no successful clinical trials of phyto-anti-COVID drugs could be conducted to date. In this article, we discuss varying perspectives on why phyto-anti-viral drug clinical trials were not successful in the case of COVID-19. The issue has been discussed in light of the usage of plant-based therapeutics in previous coronavirus outbreaks. Through this article, we aim to identify the disadvantages in this research area and suggest some measures to ensure that phytoconstituents can efficiently contribute to future random viral outbreaks. It is emphasized that if used strategically phyto-inhibitors with pre-established clinical data for other diseases can save the time required for long clinical trials. The scientific community should competently tap into phytoconstituents and take their research up to the final stage of clinical trials so that potential phyto-anti-COVID drugs can be developed.

Nitric oxide regulates watermelon (Citrullus lanatus) responses to drought stress.

The role of exogenous nitric oxide (NO) application in alleviating drought stress responses by enhancing the antioxidant activities in plants is well established for several species. However, none of the studies reported its role in protecting the watermelon genotypes from drought stress. In this study, we aimed to observe the effect of NO application on the physiological and biochemical responses of the two watermelon (Citrullus lanatus var. lanatus) genotypes grown under drought stress conditions by treating the plants with 15% polyethylene glycol 6000 (PEG 6000) and 100 µM sodium nitroprusside (SNP), which is a NO donor in Hoagland solution. Among the two genotypes, one genotype, KAR 98 was drought tolerant; while another, KAR 147 was drought sensitive. Drought stress showed a decrease in the growth parameters of both the genotypes; however, as expected it was higher in the susceptible genotype, KAR 147. NO application could not prevent the reductions in the growth parameters; however, it reduced the increment in malondialdehyde (MDA) content caused by the drought stress in both watermelon genotypes. Moreover, while drought stress condition reduced the ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), and peroxidase (POX) activities in both genotypes, NO + PEG application increased the APX activity in the tolerant genotype, KAR 98. Though the obtained results does not show the direct involvement of NO in increasing drought tolerance of watermelon plants, the increase in the APX antioxidant enzyme activity on NO application under drought stress confirmed its role in protecting the watermelon genotypes from the oxidative damage caused by the drought stress. Moreover, it can be concluded that the effect of NO application on watermelons' responses towards drought stress condition may vary according to the specific genotypes. As to date none of the studies reported the effect of NO application on the antioxidant activity of watermelon genotypes under drought stress, the present study may provide information about the mechanisms that can be focused to improve drought stress tolerance of watermelon genotypes.

Fusarium head blight in wheat: contemporary status and molecular approaches.

Fusarium head blight (FHB) disease that occurs in wheat is caused by Fusarium graminearum and is a major risk to wheat yield. Although several research efforts focusing on FHB have been conducted in the past several decades, conditions have become more critical due to the increase in its virulent forms. In such a scenario, conferring complete resistance in plants seems to be difficult for handling this issue. The phenotyping for FHB and finding a solution for it at the genetic level comprises a long-term process as FHB infection is largely affected by environmental conditions. Modern molecular strategies have played a crucial role in revealing the host-pathogen interaction in FHB. The integration of molecular biology-based methods such as genome-wide association studies and marker-based genomic selection has provided potential cultivars for breeding programs. In this review, we aim at outlining the contemporary status of the studies conducted on FHB in wheat. The influence of FHB in wheat on animals and human health is also discussed. In addition, a summary of the advancement in the molecular technologies for identifying and developing the FHB-resistant wheat genetic resources is provided. It also suggests the future measures that are required to reduce the world's vulnerability to FHB which was one of the main goals of the US Wheat and Barley Scab Initiative.

Combined Boron Toxicity and Salinity Stress-An Insight into Its Interaction in Plants.

The continuously changing environment has intensified the occurrence of abiotic stress conditions. Individually, boron (B) toxicity and salinity stress are well recognized as severe stress conditions for plants. However, their coexistence in arid and semi-arid agricultural regions has shown ambiguous effects on plant growth and development. Few studies have reported that combined boron toxicity and high salinity stress have more damaging effects on plant growth than individual B and salt stress, while other studies have highlighted less damaging effects of the combined stress. Hence, it is interesting to understand the positive interaction of this combined stress so that it can be effectively employed for the improvement of crops that generally show the negative effects of this combined stress. In this review, we discussed the possible processes that occur in plants in response to this combined stress condition. We highly suggest that the combined B and salinity stress condition should be considered as a novel stress condition by researchers; hence, we recommend the name "BorSal" for this combined boron toxicity and high salinity state in the soil. Membrane-bound activities, mobility of ions, water transport, pH changes, transpiration, photosynthesis, antioxidant activities, and different molecular transporters are involved in the effects of BorSal interaction in plants. The discussed mechanisms indicate that the BorSal stress state should be studied in light of the involved physiological and molecular processes that occur after B and salt interaction in plants.

Assessment of genetic variability for grain nutrients from diverse regions: potential for wheat improvement.

BACKGROUND: A total of 150 bread wheat genotypes representing 121 Indian and 29 Turkish origin were screened for nutrient concentrations and grain protein content. Elemental and grain protein composition were studied by Inductively Coupled Plasma-Atomic Emission Spectrophotometer and LECO analyser, respectively. The study was performed to determine the variability in nutrient concentrations present in the collected wheat genetic material from two countries. RESULTS: Several fold variations among genotypes existed for almost all the elements. Three major components of principal component analysis (PCA) revealed 60.8% variation among the genotypes. Nutrient variables segregated into two groups, one group containing all the macroelements except sulphur; and another cluster containing proteins and all the microelements except Zn and Mn. Pearson correlation analysis and heat-map were in accordance with each other determining strong positive association between P-K, Mn-Zn, Mg-S and Cu-protein content. Also, PCA and hierarchical grouping divided all the Indian and Turkish genotypes in two main clusters. CONCLUSIONS: Nutritional profile differentiated the genotypes from two countries into separate groups. However, some of the varieties were closely associated and indicated the success of global wheat exchange programs. While most of the correlations were in agreement with the previous studies, non-association of zinc with grain protein content directed towards its control by some other genetic factors. Some of the experimental wheat varieties with promising nutrient content have been suggested for future wheat advancement programs. Results obtained will be supportive for breeders involved in wheat biofortification programs, food industries and people relying on whole grain wheat products.

Extremely high boron tolerance in Puccinellia distans (Jacq.) Parl. related to root boron exclusion and a well-regulated antioxidant system.

Recent studies indicate an extremely high level of tolerance to boron (B) toxicity in Puccinellia distans (Jacq.) Parl. but the mechanistic basis is not known. Puccinellia distans was exposed to B concentrations of up to 1000 mg B L-1 and root B uptake, growth parameters, B and N contents, H2O2 accumulation and ·OH-scavenging activity were measured. Antioxidant enzyme activities including superoxide dismutase (SOD), ascorbate peroxidase, catalase, peroxidase and glutathione reductase, and lipid peroxidation products were determined. B appears to be actively excluded from roots. Excess B supply caused structural deformations in roots and leaves, H2O2 accumulation and simultaneous up-regulation of the antioxidative system, which prevented lipid peroxidation even at the highest B concentrations. Thus, P. distans has an efficient root B-exclusion capability and, in addition, B tolerance in shoots is achieved by a well-regulated antioxidant defense system.

Genetic diversity and population structure of wheat in India and Turkey.

Genetic diversity among plant species offers prospects for improving the plant characteristics. Its assessment is necessary to help tackle the threats of environmental fluctuations and for the effective exploitation of genetic resources in breeding programmes. Although wheat is one of the most thoroughly studied crops in terms of genetic polymorphism studies, phylogenetic affinities of Indian and Turkish Triticum species have not been assessed to date. In this study, genetic association of 95 tetraploid and hexaploid wheat genotypes originating from India and Turkey was determined for the first time. Combined analysis of random amplified polymorphic DNA and inter-simple sequence repeat markers disclosed 177 polymorphic bands, and both the dendrogram and two-dimensional scatterplot showed similar groupings of the wheat genotypes. Turkish hexaploid varieties were basically divided into two clusters, one group showed its close association with Indian hexaploid varieties and the other with Indian tetraploid varieties. Analysis of molecular variance revealed high (77 %) genetic variation within Indian and Turkish populations. Population structure analysis elucidated distinct clustering of wheat genotypes on the basis of both geographical origin and ploidy. The results revealed in this study will support worldwide wheat breeding programmes and assist in achieving the target of sustainable wheat production.

Mineral and heavy metal contents of the outer and inner tissues of commonly used fruits.

The rate of heavy metal pollution in some minor fruit samples growing at roadsides in Turkey were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The mineral contents of samples were found to be different depending on the several parts Citrus fruits. The highest minor and heavy metal levels for Citrus fruits were determined between 17.24 and 45.30 mg/kg boron, 2.08 and 15.05 mg/kg copper, 1.01 and 16.00 mg/kg iron and 2.35 and 9.87 mg/kg zinc. Boron content ranged from 16.54 mg/kg (Deveci pear inner pulp) to 89.89 mg/kg (Arjantin apple outer skin). The level of Fe ranged from 1.49 mg/kg (quince pulp) to 25.05 mg/kg (Ankara pear pulp). Cu content of fruits ranged between 2.52 mg/kg (Fuji apple skin) and 25.93 mg/kg quince skin). Zn content was found between 0.46 mg/kg (Golden apple pulp) and 14.34 mg/kg (quince skin). P contents ranged from 651 mg/kg (Golden apple pulp) to 1269 mg/kg (quince skin). Na was found between 500 mg/kg (Fuji apple skin) and 907 mg/kg (Arjantin apple skin).

Variation of heavy metal and micro and macro element concentrations of bread and durum wheats and their relationship in grain of Turkish wheat cultivars.

The 64 varieties displayed a large variation for all mineral elements, investigated Fe, Mn and Zn, ranging from 24.2 to 43.1 mg/kg, 27.6 to 64.8 mg/kg and 10.4 to 38.2 mg/kg, respectively. The mean Ca, K, Mg, Na, P and S concentrations in wheat rain varieties amounted to 378, 4,266, 1,183, 317, 3,513 and 1,542 mg/kg, respectively. Ca, K, Mg, Na, P and S contents of wheat varieties changed at the levels between 266 and 531 mg/kg, 3,029 and 5,566 mg/kg, 972 and 1,525 mg/kg, 277 and 368 mg/kg, 2,422 and 4,610 mg/kg and 1,241 to 2,052 mg/kg, respectively. The concentrations of Al, Cu, Fe, Mn and Zn of durum wheat samples were found at high levels. The mean Al, Cr, Mo, Ni, Cu, Fe, Mn and Zn concentrations in durum wheat varieties amounted to 10.93, 0.47, 0.72, 0.72, 5.37, 34.9, 37.28 and 20.88 mg/kg, respectively.

Comparative evaluation of some macro- and micro-element and heavy metal contents in commercial fruit juices.

Micro- and macro-element contents of several commercial fruit juices purchased from marked were determined by inductively coupled plasma atomic emission spectroscopy. Among the minor elements determined, Zn, Cu, Mn, Mo, Co, Cd and Ni were found to be lover. Major mineral contents of fruit juices were established as Ca, K, Mg and P. The potassium contents of fruit juices were determined at the higher levels. K contents of fruit juices ranged between 475 mg/kg (B apricot) and 1478 mg/kg (B peach). In addition while Ca contents of fruit juices change between 19.3 mg/kg (E cherry) and 81.8 mg/kg (C orange), Mg contents ranged at the levels between 23.7 mg/kg (A apricot) and 65.4 mg/kg (D orange). Generally Ca and contents of peach, orange and apricot juices that belong to A and D companies were determined at the high levels.

Mineral and heavy metal levels of some fruits grown at the roadsides.

The rate of heavy metal pollution of some minor fruit samples growing at the roadsides in Turkey were determined by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES). Pb, Zn and Cu were found at the high levels in the fruit samples. The results showed that the average level of Cu changed between 0.27 mg/kg (Sample 11) and 0.05 mg/kg (Sample 15), Cr 0.32 mg/kg (Sample 14) and 0.18 mg/kg (Sample 13), Ni 0.68 mg/kg (Sample 12) and 0.26 g/kg (Sample 15), Pb 2.86 mg/kg (Sample 12) and 1.54 mg/kg (Sample 4) and Se 12.96 mg/kg (Sample 14) and 5.42 mg/kg (Sample 7). The levels of Cu, Cd and Cr in samples do not appear to reach pollution levels.

Removal of boron from aqueous solution by using neutralized red mud.

The adsorptive removal of boron from aqueous solution by using the neutralized red mud was studied in batch equilibration technique. The effects of pH, adsorbent dosage, initial boron concentration and contact time on the adsorption were investigated. The experiments demonstrated that boron removal was of a little fluctuation in pH range of 2-7 and it takes 20 min to attain equilibrium. The adsorption data was analyzed using the Langmuir and the Freundlich isotherm models and it was found that the Freundlich isotherm model represented the measured sorption data well.

Determination of minerals extracted from several commercial teas (Camellia sinensis) to hot water (infusion).

Mineral contents of some tea and their infusions drunk in Turkey were established by inductively coupled plasma atomic emission spectrometry. The Al, Ca, K, Mg, Mn, P, and S contents were very high in both infusions and tea (i.e., pieces of the tea plant). The As, Cd, Cr, Li, Pb, and Se contents of infusion and tea were found to be very low. The level of K of all samples is higher than those of other minerals. Generally, mineral contents of tea were found to be higher than those of tea infusions. In addition, the health benefits of teas and knowledge of their mineral contents are of great interest and may be useful for further study of enzyme systems and vital biochemical functions.